Gfap, short for glial fibrillary acidic protein, is an astrocytic cytoskeletal protein. It is involved in maintaining the structural integrity of astrocytes in the central nervous system. Although its exact associated pathways are not comprehensively detailed in the provided references, it is clear that it holds significance in neurodegenerative processes [1,3,4,5,6,7,8,9,10]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, could potentially offer valuable insights into its function in vivo.

In Alzheimer's disease, studies have shown that blood Gfap levels are higher in the Aβ-positive group, as well as in individuals with Alzheimer's disease (AD) or mild cognitive impairment (MCI) compared to healthy controls, suggesting its potential as a biomarker for early-stage AD [1]. Plasma Gfap is an early marker associated with brain amyloid-β pathology but not tau aggregation, even in cognitively normal individuals with a normal amyloid-β status, and it may promote tau accumulation secondary to amyloid-β aggregation [3].

In autoimmune Gfap astrocytopathy, over half of the patients presented with movement disorders, autonomic dysfunction, and hyponatremia [2].

In astrocytoma, Gfap is a classical marker, but its heterogeneous expression may mask its correlation with malignancy grade, and discriminating between its isoforms may improve the accuracy of assessing the differentiation state [5].

Additionally, peripheral Gfap is a potential biomarker for the early diagnosis of dementia [6], and it can help distinguish AD from frontotemporal dementia (FTD) and neurodegenerative dementias from healthy controls, though with lower accuracy than p-tau181 and NfL [7].

In traumatic brain injury, day-of-injury plasma Gfap concentrations have good to excellent prognostic value for predicting death and unfavourable outcome [8].

In acute coma, increased Gfap plasma concentrations can identify intracranial hemorrhage with high diagnostic accuracy [10].

Alexander disease is caused by dominantly acting mutations in Gfap, leading to a gain-of-function sometimes referred to as "Gfap toxicity" [9].

In conclusion, Gfap is crucial for the structural integrity of astrocytes. Model-based research, especially through KO/CKO mouse models which could potentially be used in future studies, may further clarify its role. The current research reveals its significance in multiple disease areas, including Alzheimer's disease, autoimmune disorders, astrocytoma, dementia, traumatic brain injury, acute coma, and Alexander disease. Understanding Gfap can provide new perspectives for disease diagnosis, prognosis, and treatment.